This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The ubiquitin proteasome system (UPS) is made up of a sequentially acting set of enzymes termed E1 (ubiquitin activating enzyme), E2 (ubiquitin conjugating enzyme), and E3s (ubiquitin ligase). The action of the UPS cascade is responsible for the elimination of ubiquitinated proteins including many that regulate cell cycle progression. The phosphorylation of cell cycle substrates allows for their recognition by a subset of E3 enzymes. Polyubiquitin chains are then added to the substrate which targets them to the 26S proteasome for degradation. In my lab we are interested in understanding the catalytic mechanism of ubiquitin transfer, the mechanism by which UPS components are regulated and the mechanism by which E3 enzymes recognize their substrates.